A well-known adage is that necrotizing fasciitis, which is colloquially abbreviated to “nec-fasc,” is a rapidly progressive and often fatal disease that proves difficult to diagnose.
Nomenclature and Background Information
Necrotizing fasciitis is a subset of a larger group of diseases known as necrotizing soft tissue infections or NSTIs. In this blog post, the term NSTI will be used in an effort to be inclusive of infection that may be affecting the muscles (myositis), deeper dermis and subcutaneous tissue (cellulitis) or fascia (fasciitis).
The first known reference to the disease process can be traced back to the 5th century; Hippocrates, who is often referred to as the father of medicine, wrote, “[m]any were attacked by the erysipelas all over the body when the exciting cause was a trivial accident…flesh, sinews, and bones fell away in large quantities…there were many deaths.” The description from over two thousand years ago still holds true today, and although NSTIs are rare, the average mortality reported has been around 20% in the past 20 years (ranging from 15% to 45%, depending on the study examined).
Classification
The types of NSTIs can be classified either by anatomical location (i.e. most commonly affects the extremities, or, if there is perineal, genital and perianal involvement, it is known as Fournier gangrene) or bacterial involvement (divided into the following types).
- Type 1: polymicrobial (aerobic and anaerobic) – more common than type 2
- elderly patients, comorbidities (DM, ulcers), previous surgical intervention
- Type 2: monomicrobial (Group A streptococcus, MRSA)
- in any age group and even patients without underlying disorders
- 50% of cases have no clear portal entry
- Type 3: gas gangrene (Clostridium sp.)
Risk Factors
Although NSTIs can occur in patients without significant medical disease, there are definite risk factors that increase one’s chance of developing an NSTI:
- patient-related factors: diabetes mellitus, obesity, peripheral arterial disease, chronic alcohol abuse, immunosuppression, malignancy, end-stage renal disease
- barrier integrity-related factors: cutaneous lesions like insect bites or penetrating trauma, injection drug use, surgical incisions (for example, neonatal circumcision), mucosal breach (such as hemorrhoids, episiotomy)
Sign and Symptoms
- hard signs (note that only 1/3rd of patients may present with these “textbook” signs): bullae, crepitus, violaceous hue, “dishwater” discharge
- systemic signs: low-grade fever with tachycardia (out of proportion to the fever)
- other non-specific signs: malaise, myalgias, diarrhea, anorexia
- edema, brownish skin discoloration, decreased sensation in affected limb, a sense of heaviness
- PEARL: make sure to mark the borders of the erythema to track progression
- mental status changes (delirium, irritability)
In an article titled, “Pitfalls in Diagnosing Necrotizing Fasciitis,” Table 2 outlines the evolution of physical signs from early to late disease.
Diagnosis
The gold standard for diagnosis is via surgical exploration; however, in order to get a patient to surgery in a timely fashion, there are important tests that can raise suspicion that there is an underlying NSTI.
In laboratory tests, the following findings may be suggestive of NSTI, but there is no one specific sign that would be pathognomonic. A patient may have metabolic acidosis, coagulopathy, leukocytosis with left shift, anemia, thrombocytopenia, elevated CRP/ESR, myoglobinuria, signs of renal or hepatic dysfunction, and interestingly, hyponatremia and well as hyperlactatemia.
One notable finding is that elevated serum CK or AST concentrations suggest deep infection involving muscle or fascia rather than more superficial cellulitis. Furthermore, another source considered the utility of trending procalcitonin levels as a representation of adequate infection source control.
In terms of imaging tests, radiography can be useful but is not a necessity. If suspicion for NSTI is high, patient should immediately be sent to surgery. The best imaging modality is CT, and the presence of gas is nearly pathognomonic. Other signs suggestive of NSTI may be:
- presence of fluid collections or abscess
- heterogeneity or absence of tissue enhancement
- edema at or below level of fascia
LRINEC (Laboratory Risk Index) Score
While there is a score for screening NSTIs, known as the Laboratory Risk Index, it has not been externally validated as of 2017. Nevertheless, looking at the components of the score on MDCalc gives a clinician an idea of what type of parameters might be of interest in diagnosing necrotizing soft tissue infections.
The LRINEC score determined that the laboratory findings of interest are: CRP, WBC, hemoglobin, sodium, creatinine and glucose. The score has “high specificity but low sensitivity” – what does this mean? This means that if your LRINEC score is low or normal, this does not rule out an NSTI; however, if it is 6 or higher, that raises the suspicion and further workup is recommended.
Differential diagnosis
- cellulitis
- dermatological rash (contact dermatitis)
- pyoderma gangrenosum
- pyomyositis
- deep vein thrombosis
- calciphylaxis (cutaneous manifestations)
Treatment
The two pillars of treatment are surgery and antibiotics.
Broad spectrum antibiotics should be given intravenously as soon as necrotizing infection is suspected, but only aftertwo sets of blood cultures have been taken. The antibiotic of choice, according to Tintinalli’s Emergency Medicine Manual (8th) edition are the following:
- vancomycin 1 gram IV every 12 hours PLUS meropenem 500 to 1000 mg IV every 8 hours
- alternatively: vancomycin (same regimen) PLUS piperacillin/tazobactam 4.5 gram IV every six hours
- clindamycin can be added to the regimen (mechanism of action: inhibits toxin synthesis)
Surgical debridement is key. In severe cases, surgery will need to be radical and aggressive to ensure optimal outcomes and include fasciotomy or even amputation.
Other considerations:
- aggressive intravenous fluid resuscitation (IV crystalloids)
- may consider: blood transfusion (if hemolysis results in severe anemia)
- may consider: tetanus prophylaxis (based on mechanism of injury)
Mortality
Certain clinical characteristics have been associated with higher mortality; these vary by study; the list below compiles the features that are frequently mentioned across the board:
- advanced age
- female sex
- multiple comorbidities
- sepsis upon presentation
Potential Treatment Delays
Treatment of NSTIs is unequivocally surgical debridement, but unfortunately surgery doesn’t always happen within 24 hours. There are a few factors that inhibit prompt treatment, which can be broken into three larger categories: patient delay (not seeking care early enough), physician delay (not recognizing the signs) and system delay (logistical issues within a hospital system). Issues in one or all of these categories can result in catastrophic outcomes.
Two out of these three categories are outside a physician’s control; however, with thorough training and continuing medical education, we can work to minimize the cases in which the delay is due to a “missed diagnosis” on the part of the clinician.
Tips for Recognizing NSTIs Early
Always maintain a high index of suspicion. What does that mean? It means that the threshold for considering (and ruling out) necrotizing soft tissue infections needs to be low.
Host of the Trauma ICU Rounds podcast Dr. Dennis Kim stated that for him, a patient who presents with soft tissue infection with swelling, erythema, pain out of proportion (POOP) to physical exam with systemic symptoms is enough to consider a surgical consultation.
Although knowing the classic signs and symptoms of necrotizing soft tissue infections is paramount to a timely diagnosis, it is prudent to keep in mind that not all cases will present “classically.”
Here are some important considerations:
- patient need not have comorbidities to develop an NSTI
- fever may be absent; this could be due in part to use of over-the-counter NSAIDs
- although classically associated with a break in the skin, bacteria can travel hematogenously from other sites (like Streptococcal pharyngitis)
- in fact, patient may not have cutaneous manifestations superficially
- infection can be acute (developing over hours) but can also be indolent (like in DM foot ulcers)
- pain out of proportion in what appears to be a simple cellulitis should raise warning bells
References and Further Reading
- Goh T, Goh LG. Pitfalls in diagnosing necrotizing fasciitis. Patient Safety Network. https://psnet.ahrq.gov/web-mm/pitfalls-diagnosing-necrotizing-fasciitis. Published August 21, 2014. Accessed September 1, 2021.
- Ho, Wong Chin. MDCalc: LRINEC Score for Necrotizing Soft Tissue Infection. LINK
- Kim, D. (Host). (2021, June 07). Necrotizing Soft Tissue Infections (No. 39) [Audio podcast episode]. In Trauma ICU Rounds. Surgery Academix Corps. LINK
- Nawijn, F., Smeeing, D.P.J., Houwert, R.M. et al. Time is of the essence when treating necrotizing soft tissue infections: a systematic review and meta-analysis. World J Emerg Surg 15, 4 (2020). https://doi.org/10.1186/s13017-019-0286-6
- Stevens D. Necrotizing soft tissue infections. UpToDate. https://www.uptodate.com/contents/necrotizing-soft-tissue-infections#H1. Published August 25, 2021. Accessed September 2, 2021.
- Tintinalli, Judith E, and David Cline. Tintinalli’s Emergency Medicine Manual (8th ed.). New York: McGraw-Hill Medical, 2017.
